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Preschoolers commonly experience symptoms of ADHD and disruptive behavior problems. Behavioral parent management training (PMT) is an evidence-based intervention for addressing both ADHD and disruptive behaviors in this population; however, many PMT programs are burdensome in length and have limited data regarding long-term effectiveness for ADHD specific outcomes. This study examined outcomes up to 1 year following completion of a brief behavioral intervention (M = 6.51 sessions) for preschoolers. Participants were children aged 2-6 years with clinically significant disruptive behaviors and their parents. Results demonstrated significant improvements in parent-reported child hyperactivity and inattention from pre-to-post intervention, with sustained improvement at 6 months and 1 year post intervention. Teacher-reported hyperactivity and inattention also showed significant improvements from pre-to-post intervention, which were maintained across time points. These results were also found among a subset of participants with clinically significant ADHD symptoms at baseline. This study highlights the long-term effectiveness of a brief PMT program to address symptoms of ADHD and disruptive behaviors in preschoolers. Findings support the recommendation to offer PMT as a first-line intervention for preschoolers with ADHD symptoms to reduce the need for early intervention with stimulant medication and address comorbid disruptive behaviors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An estimated 1.8% of U.S. adolescents identify as transgender, and when using expansive language to include diverse identities along the gender continuum (e.g., nonbinary, gender fluid), rates may be notably higher. Gender-diverse youth (GDY) experience significantly elevated rates of depression, anxiety, suicidality, and eating disorders relative to the general population. Youth with autism spectrum disorders also appear to report diverse gender identities at higher rates than neurotypical youth. Gender-minoritized stress, including distal (e.g., transgender related stigma and discrimination) and proximal (e.g., social or familial rejection due to gender-diverse identity) stressors, increase risk for mental health disorders among GDY, and gender affirmation mitigates risk. Gender-affirming medical and behavioral health care is associated with enhanced resilience and positive mental health outcomes for GDY.

RASopathies are a group of genetic disorders that are caused by genes that affect the canonical Ras/mitogen-activated protein kinase (MAPK) signaling pathway. Despite tremendous progress in understanding the molecular consequences of these genetic anomalies, little movement has been made in translating these findings to the clinic. This year, the seventh International RASopathies Symposium focused on expanding the research knowledge that we have gained over the years to enhance new discoveries in the field, ones that we hope can lead to effective therapeutic treatments. Indeed, for the first time, research efforts are finally being translated to the clinic, with compassionate use of Ras/MAPK pathway inhibitors for the treatment of RASopathies. This biannual meeting, organized by the RASopathies Network, brought together basic scientists, clinicians, clinician scientists, patients, advocates, and their families, as well as representatives from pharmaceutical companies and the National Institutes of Health. A history of RASopathy gene discovery, identification of new disease genes, and the latest research, both at the bench and in the clinic, were discussed., (© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

It has been estimated that 10-15% of people with Robinow syndrome (RS) show delayed development, but no studies have formally assessed developmental domains. The objective of this study is to provide the first description of cognitive, adaptive, and psychological functioning in RS. Thirteen participants (10 males) aged 4-51 years were seen for neuropsychological screening. Eight had autosomal-dominant RS (DVL1, n = 5; WNT5A, n = 3), four had autosomal-recessive RS (NXN, n = 2; ROR2, n = 2), and one had a mutation on an RS candidate gene (GPC4). Participants completed measures of intellectual, fine-motor, adaptive, executive, and psychological functioning. Findings indicated generally average intellectual functioning and low-average visuomotor skills. Adaptive functioning was average in autosomal-recessive RS (RRS) but low average in autosomal-dominant RS (DRS). Parent-report indicated executive dysfunction and attention problems in 4/8 children, 3/4 of whom had a DVL1 variant; adult self-report did not indicate similar difficulties. Learning disabilities were also reported in 4/8 individuals with DRS, 3/4 of whom had a DVL1 variant. Peer problems were reported for a majority of participants, many of whom also reported emotional concerns. Altogether, the findings indicate average neurocognitive functioning in RRS. In contrast, DRS, especially DVL1 pathogenic alleles, may confer specific risk for neurodevelopmental disability., (© 2020 Wiley Periodicals LLC.)

While challenges related to health care utilization among transgender individuals have been discussed, studies examining health services under Medicaid are limited. A retrospective review was performed on all patients who presented with Gender Dysphoria from 2013-2018 to one Medicaid managed program. Utilization rates of distinct services and interventions were analyzed. A total of 192 patients, with 787 encounters, were identified. Mean patient age was 15 years old. Mean number of encounters per patient was 4.1. The average number of distinct specialties seen was 1.4. Behavioral health (BH) services were most commonly utilized (50%). Endocrinology and surgical services were encountered less frequently. Medications were prescribed for 25% of patients; hormonal treatment was prescribed for 6.7%. This study highlights the deficiencies in services this population is receiving under one managed Medicaid program. While behavioral health services are widely employed, underutilization of medical and surgical consultations compromises patient awareness of available interventions.

Most children with hypothalamic hamartoma (HH) manifest symptoms of epilepsy and associated cognitive deficits and behavioral difficulties as well as central precocious puberty (CPP). However, there is little to no research examining behavioral difficulties in children with HH without epilepsy, nor is there research examining treatments to address the behavioral difficulties of patients with HH without epilepsy. In the current case report, the authors implemented a validated parent management training program [the Brief Behavioral Intervention (BBI)], to treat symptoms of ADHD and disruptive behavior in a 6-year-old female patient with HH and CPP. The family participated in six BBI sessions over a period of 8 weeks. Parent behavioral ratings suggested significant reductions of symptoms of ADHD and disruptive behaviors to the normal range. The current case report demonstrates the effectiveness of the BBI program in the treatment of behavioral difficulties in a patient with HH and CPP. Further, the present study explores behavioral manifestations rarely explored in patients with HH without epilepsy.

Dysregulation of the mitogen activated protein kinase (MAPK) pathway in Costello syndrome (CS) may contribute to increased risk for autism-spectrum disorder (ASD). We examined prevalence of ASD symptoms in 14 individuals (six females) age 1-18 years with molecularly confirmed CS. Caregivers completed the Modified Checklist for Autism in Toddlers (M-CHAT) for ages 0-4 years (n = 7), and the Social Communication Questionnaire (SCQ) for ages 4 and older (n = 7). Age was associated with meeting ASD criteria: 5/7 (71.4%) younger children met the ASD cut-off on the MCHAT, compared to 0/7 older children on the SCQ. The following medical and developmental factors were strongly associated with ASD criteria on the M-CHAT: having a gastrostomy tube at time of assessment, not eating solid food, not walking, and not being toilet trained. Two children who met stricter ASD criteria had significantly lower adaptive functioning and were physically much more impaired. Among older participants, SCQ subscale scores in communication, socialization, and repetitive behavior domains were comparable to the typically-developing normative sample. ASD symptoms were highly elevated in younger CS individuals. Older children did not differ from typically developing samples in prevalence of ASD symptoms. CS individuals may appear to fall on the autism spectrum in early childhood due to severe feeding and orthopedic problems that improve by age four, suggesting many of these children may eventually emerge out of an ASD presentation., (© 2017 Wiley Periodicals, Inc.)

Several different conceptualizations of Oppositional Defiant Disorder (ODD) symptoms have been proposed, including one undivided set of symptoms (DSM-IV-TR; APA 2000); two domains of symptoms subdivided into affective and behavioral; and three domains of symptoms subdivided as angry/irritable, argumentative/defiant, and spiteful. The current study utilizes a novel approach to examining the division of ODD symptoms through use of network analysis. Participants were 109 preschoolers (64 male) between the ages of three and six (M = 4.34 years, SD = 1.08) and their parents and teachers/caregivers, who provided ratings of ODD symptoms. Results are consistent with one-, two-, and three- cluster solutions of ODD, but perhaps provide most support for the three-cluster solution. In addition, results support the idea that negative affect, particularly anger, forms the core of the ODD symptom network during preschool. These results suggest the importance of targeting anger in preschool interventions for ODD.

This study examines the impact of maternal depression on reductions in children's behavior problems severity following implementation of the Brief Behavioral Intervention-a brief, manualized parent management training treatment. The parents of 87 children aged 2-6 years of age received parent management training at a metropolitan hospital. Parents of participants completed measures of externalizing behavior and maternal depression. The association between pre-post treatment change in externalizing behavior and maternal depression was examined using an autoregressive cross-lagged model. Results showed that self-reported maternal depressive symptoms at pre-treatment negatively influenced the overall magnitude of reduction of reported externalizing behaviors in children following treatment. Results indicate that aspects of family functioning not specifically targeted by parent management training, such as maternal depression, significantly affect treatment outcomes. Clinicians providing parent management training may benefit from assessing for maternal depression and modifying treatment as indicated.

DK phocomelia/von Voss Cherstvoy syndrome is a rare condition characterized by upper limb and urogenital abnormalities and various brain anomalies. Previously reported cases have noted significant developmental delays, although no formal testing of cognitive abilities has been reported. In this paper we describe results from a comprehensive neuropsychological evaluation of a 12-year-old male with DK phocomelia syndrome. Test findings indicated mild impairment in intellectual functioning, with more significant impairment in adaptive skills and academic achievement. The neuropsychological profile converged with neurological findings, showing a distinct pattern of strengths and weaknesses that suggests functional compromise of posterior brain regions with relatively well-preserved functioning of more anterior regions. Specifically, impairments were evident in perceptual reasoning, visual perception, and visuomotor integration, whereas normal or near normal functioning was evident in memory, receptive language, social cognition, attention, and most aspects of executive functioning. To our knowledge this is the first report to describe the neurocognitive profile of an individual with DK phocomelia syndrome., (© 2015 Wiley Periodicals, Inc.)

The impact of diabetes on the developing brain is well-accepted. Effects on neurocognitive functioning are moderate but have larger functional implications, especially when considered through a developmental lens. Pathophysiological factors such as severe hypoglycemia and chronic hyperglycemia can alter developmental trajectories in early childhood and perhaps at later periods. In this paper, we selectively review neurocognitive outcomes in pediatric diabetes (largely type 1), integrating recent research from developmental neuroscience and neuroimaging. We examine the effects of diabetes at different stages and place findings within a neurodevelopmental diathesis/stress framework. Early-onset diabetes is associated with specific effects on memory and more global cognitive late-effects, but less is known about cognitive outcomes of diabetes in later childhood and in adolescence, a time of increased neurobehavioral vulnerability that has received relatively limited empirical attention. Studies are also needed to better elucidate risk and protective factors that may moderate neurodevelopmental outcomes in youth with diabetes.

Objective: To determine whether impairments in neurocognitive functioning are detectable at type 1 diabetes diagnosis and associated with subsequent glycemic control., Research Design and Methods: Children/adolescents (N = 147) aged 5-18 years completed neuropsychological testing during their inpatient hospitalization for new-onset type 1 diabetes. Test scores were compared with normative data using one-sample Student t tests. Children with onset before 8 years of age were compared with children aged 9-18 years using ANOVA, and associations between neurocognitive performance at diagnosis and glycemic control 1 year postdiagnosis were examined using regression analyses., Results: Children with type 1 diabetes performed significantly below expectations on most neurocognitive measures (P values <0.0001), with large decrements from the normative mean evident in psychomotor speed (>1 SD), visuomotor integration (0.7 SD), and phonemic fluency (0.8 SD). High incidence of impairment (scores less than second percentile) was evident on all tasks except digit span. Dominant-hand psychomotor speed was significantly associated with poor glycemic control (A1C ≥9.5% [80 mmol/mol]; P = 0.032) 1 year postdiagnosis, controlling for race/ethnicity, sex, and reading ability. Impaired psychomotor speed was associated with a 0.77% increase in mean A1C (8.4 mmol/mol)., Conclusions: Deficits were evident in neurocognitive functioning within days of diabetes diagnosis that were associated with diabetes outcomes over 1 year postdiagnosis. Impairment was most apparent in psychomotor speed, consistent with research implicating damage to posterior white matter tracts and associated gray matter regions in type 1 diabetes. Psychomotor impairment may be an early marker for a broader neurobehavioral vulnerability that has implications for long-term diabetes management., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: The aim of this study was to develop and validate a psychosocial screening tool to predict risk for poor glycemic control in children with type 1 diabetes., Methods: Participants seen for psychological screening were 196 children aged 3-18 yr at diabetes diagnosis. A psychosocial risk index was developed to predict poor glycemic control [mean hemoglobin A1c (HbA1c) ≥ 9.5%; 80 mmol/mol] 1-4 yr post diagnosis. Cutoff scores were derived for multiple levels of risk from receiver operating characteristic (ROC) curves and likelihood ratios (LRs). Discrimination and calibration were examined in the sample, and validated in 1000 bootstrap samples. Ability to predict diabetes-related emergency-room (ER) visits and diabetic ketoacidosis (DKA) was also tested., Results: The risk index accounted for 16.2% of variance in mean HbA1c, discriminated between children with and without poor glycemic control [area under the receiver operating characteristic curve (AUC) = 0.814, 0.713-0.915; p < 0.001], ER visits (AUC = 0.655, 0.561-0.748; p = 0.001), and DKA(AUC = 0.709, 0.588-0.830; p = 0.001), and was well-calibrated. Every one-point increase in score was associated with an absolute increase in risk for poor glycemic control of approximately 10% (LRs = 1.7, 3.2, 5.8, and 9.3). Sensitivity and specificity were 0.68 (0.43-0.86) and 0.79 (0.72-0.84) for detecting patients at moderate risk, and 0.53 (0.29-0.75) and 0.91 (0.85-0.95) for detecting high-risk patients. The index performed equally well in validation samples., Conclusions: This paper presents the first psychosocial risk index for poor glycemic control in children newly diagnosed with type 1 diabetes. It is brief, easily administered, and provides a single score that translates directly into an estimate of risk that can help guide routine diabetes care., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Costello syndrome (CS) is a rare genetic disorder caused by germline mutations in the HRAS proto-oncogene which belongs to the family of syndromes called rasopathies. HRAS plays a key role in synaptic long-term potentiation (LTP) and memory formation. Prior research has found impaired recall memory in CS despite enhancement in LTP that would predict memory preservation. Based on findings in other rasopathies, we hypothesized that the memory deficit in CS would be specific to recall, and that recognition memory would show relative preservation. Memory was tested using word-list learning and story memory tasks with both recall and recognition trials, a design that allowed us to examine these processes separately. Participants were 11 adolescents and young adults with molecularly confirmed CS, all of whom fell in the mild to moderate range of intellectual disability. Results indicated a clear dissociation between verbal recall, which was impaired (M = 69 ± 14), and recognition memory, which was relatively intact (M = 86 ± 14). Story recognition was highly correlated with listening comprehension (r = 0.986), which also fell in the low-average range (M = 80 ± 12.9). Performance on other measures of linguistic ability and academic skills was impaired. The findings suggest relatively preserved recognition memory that also provides some support for verbal comprehension. This is the first report of relatively normal performance in a cognitive domain in CS. Further research is needed to better understand the mechanisms by which altered RAS-MAPK signaling affects neuronal plasticity and memory processes in the brain., (Copyright © 2013 Wiley Periodicals, Inc.)

Parent management training is an evidence-based treatment for disruptive behavior. However, the number of treatment sessions can be high, contributing to high attrition rates. The purpose of this study was to examine post-treatment, 6-month, and 1-year treatment outcomes of the Brief Behavioral Intervention. One hundred twenty children aged 2-6.5 years demonstrating clinically significant disruptive behavior were referred to an outpatient clinic for treatment and participated in the study. Attrition was below reported rates in the literature. Significant decreases in child disruptive behavior and parent stress were found from pre-to-post intervention, and improvements were maintained at follow-ups. Significant pre-to-post intervention teacher reported decreases in behavior were reported.

Objectives: To catalogue patients with DSD and to assess the concordance of genotype and phenotype with sex assignment at birth compared to sex assignment before and following assessment by a Gender Medicine Team (GMT) at one institution, as an initial step in formulating standardized guidelines for management of these conditions., Design: After obtaining IRB approval, a retrospective chart review was conducted patients seen in the Gender Medicine Clinic (GMC) between 2006-2009 at Texas Children's Hospital (TCH), Houston, Texas. McNemar's test and Kappa agreement provided associations of various factors with sex assignment at birth prior to GMT assessment and after GMT assessment., Participants: Forty-seven patients seen in the GMC with confirmed DSD., Results: Forty-seven patients met the inclusion criteria. The mean age of the patients at the time of GMT evaluation was 9.1+/-6.1 years; 61.7% had male karyotype, and 38.3% had female karyotype; 51.1% had a male external phenotype, 42.6% had a female external phenotype, and 6.4% had phenotypic ambiguity. Sex assignment was concordant with genotype and phenotype in 63.8% and 86.4%, respectively of cases at the time of birth and in 76.6% and 97.7%, respectively, of cases after assessment by GMT., Conclusion: Long-term outcomes are needed to establish standardized practice guidelines for decision-making.

Children born with disorders of sexual differentiation (DSD) pose numerous challenges for the parents, family, and treating physicians. The pediatrician is usually the first medical contact for newborns with DSD or for toddlers and children who present with DSD at a later time. Several years ago, we formed a Gender Medicine Team (GMT) at Baylor College of Medicine and Texas Children's Hospital (TCH) to explore and evaluate the most appropriate management strategies, which had long been a matter of concern and contention. Subsequently, the GMT, composed of experts in the fields of endocrinology, ethics, genetics, gynecology, psychology, pediatric surgery, and urology, formed a Task Force to evaluate the information available from our own experiences and from reviews of the literature. Utilizing the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system to assess the evidence and recommendations, the Task Force developed a consensus statement for clinical management of DSD and for making appropriate sex assignments., (Copyright 2012, SLACK Incorporated.)

The primary aims of this exploratory study were to determine the rate of occurrence of acute stress disorder (ASD) in children newly diagnosed with Type 1 diabetes and their parents, to examine relationships with demographic and psychosocial factors, and to examine the relationships between ASD symptom clusters and early adherence behavior (clinic attendance). The sample consisted of 102 parents of children ages 0-17 years and 40 youth ages 11-17 who were evaluated within three days of diabetes diagnosis. Eighteen percent of parents and 17% of youth reported subthreshold symptoms of ASD. Acute stress symptoms and demographic variables predicted clinic attendance, with a differential pattern evident in the responses of youth and their parents. These findings reinforce the importance of screening symptoms of ASD in youth with newly diagnosed diabetes and their parents to assist in identifying families who may be in need of additional support.

Costello syndrome is a rare rasopathy resulting from germline mutations of the proto-oncogene HRAS. Its phenotype includes severe failure-to-thrive, cardiac abnormalities, a predisposition to benign and malignant tumors, hypotonia, and developmental delay. Costello syndrome is associated with cognitive impairment, including intellectual functioning generally in the mild to moderate range of disability, commensurate adaptive functioning, and increased anxiety. Relative strengths have been found for nonverbal fluid reasoning (FR). Gender effects have been reported, with females showing better adaptive functioning across domains. Developmentally, nonverbal skills plateau in late childhood/early adolescence, whereas the rate of vocabulary acquisition may increase in adolescence into early adulthood. Here we review the literature assessing cognitive, adaptive, and behavioral functioning in Costello syndrome, and we provide data from an ongoing longitudinal study. Severity of cognitive impairment may depend upon the specific HRAS mutation, as three individuals with the p.G13C change showed average nonverbal FR skills and borderline-to-low average overall nonverbal IQ. Further, separation anxiety is more common in Costello syndrome than in the general population, affecting 39% of this cohort, and males are more often overly anxious than females. Interrelations between anxiety and cognitive and adaptive functioning were found, pointing to functional difficulties as a likely source of stress and anxiety. Taking into account data from animal models, cognitive and behavioral changes likely originate from abnormal differentiation of neuronal precursor cells, which result in structural and functional brain differences., (2011 Wiley-Liss, Inc.)

Costello syndrome is characterized by severe failure-to-thrive, short stature, cardiac abnormalities (heart defects, tachyarrhythmia, and hypertrophic cardiomyopathy (HCM)), distinctive facial features, a predisposition to papillomata and malignant tumors, postnatal cerebellar overgrowth resulting in Chiari 1 malformation, and cognitive disabilities. De novo germline mutations in the proto-oncogene HRAS cause Costello syndrome. Most mutations affect the glycine residues in position 12 or 13, and more than 80% of patients share p.G12S. To test the hypothesis that subtle genotype-phenotype differences exist, we report the first cohort comparison between 12 Costello syndrome individuals with p.G13C and individuals with p.G12S. The individuals with p.G13C had many typical findings including polyhydramnios, failure-to-thrive, HCM, macrocephaly with posterior fossa crowding, and developmental delay. Subjectively, their facial features were less coarse. Statistically significant differences included the absence of multifocal atrial tachycardia (P-value = 0.033), ulnar deviation of the wrist (P < 0.001) and papillomata (P = 0.003), and fewer neurosurgical procedures (P = 0.024). Fewer individuals with p.G13C had short stature (height below -2 SD) without use of growth hormone (P < 0.001). The noteworthy absence of malignant tumors did not reach statistical significance. Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair resulting in easily pluckable hair with a matted appearance, different from the tight curls typical for most Costello syndrome individuals. Unusually long eye lashes requiring trimming are a novel finding we termed dolichocilia. These distinctive ectodermal findings suggest a cell type specific effect of this particular mutation. Additional patients are needed to validate these findings., (Copyright © 2011 Wiley-Liss, Inc.)

Objective: Psychosocial screening has been recommended for pediatric patients with newly diagnosed type 1 diabetes and their families. Our objective was to assess a psychosocial screening protocol in its feasibility, acceptability to families, and ability to predict early emerging complications, nonadherent family behavior, and use of preventive psychology services., Research Design and Methods: A total of 125 patients and their caregivers were asked to participate in a standardized screening interview after admission at a large urban children's hospital with a new diagnosis of type 1 diabetes. Medical records were reviewed for subsequent diabetes-related emergency department (ED) admissions, missed diabetes clinic appointments, and psychology follow-up within 9 months of diagnosis., Results: Of 125 families, 121 (96.8%) agreed to participate in the screening, and a subsample of 30 surveyed caregivers indicated high levels of satisfaction. Risk factors at diagnosis predicted subsequent ED admissions with a sensitivity of 100% and a specificity of 98.6%. Children from single-parent households with a history of behavior problems were nearly six times more likely to be seen in the ED after diagnosis. Missed appointments were likeliest among African Americans, 65% of whom missed at least one diabetes-related appointment. Psychology services for preventive intervention were underutilized, despite the high acceptability of the psychosocial screening., Conclusions: Psychosocial screening of newly diagnosed patients with type 1 diabetes is feasible, acceptable to families, and able to identify families at risk for early emerging complications and nonadherence. Challenges remain with regards to reimbursement and fostering follow-up for preventive care.

Nonadherence to different aspects of the diabetes regimen is common. Problems early in the course of illness predict later difficulties with nonadherence; conversely, good management early on protects against later complications. Screening for early risk factors at the time of diabetes diagnosis is therefore critical for promoting the health of children with type 1 diabetes. The purpose of this paper is to review and synthesize the recent empirical literature on early risk factors for nonadherence in type 1 diabetes, with a focus on three specific adherence behaviors: insulin administration, blood glucose monitoring, and clinic attendance. Risk factors are considered within several broad categories: sociodemographic barriers that limit access to care; child and parent factors that affect adherence both directly and indirectly via their impact on the development of family teamwork; and family interactions with their health-care providers. We integrate the different findings into a "simple model" that can be used to develop efficient screening protocols that can in turn guide efforts at preventive intervention.

Clinical and molecular analyses of Costello syndrome are proceeding at a rapid pace, including the delineation of the adult phenotype. We designed a two-part survey in order to describe the quality of life (QoL) of older individuals with Costello syndrome. The survey consisted of the Costello syndrome quality of life (CSQoL): Caregiver Questionnaire, to obtain objective information such as skills, activities, and medical issues from caregivers; and the CSQoL:Self-Questionnaire assessing subjective information including self-esteem, life satisfaction, and interpersonal relations from affected individuals. Thirteen of 18 (72%) individuals with Costello syndrome (age 16-34 years, mean 22 years) and caregiver pairs responded. The data were analyzed to study day-to-day life, and to determine potential impediments on QoL for older individuals with Costello syndrome. The CSQoL:Caregiver total scores were significantly lower than the CSQoL:Self total scores as demonstrated by the Wilcoxon Signed Ranks Test (P < 0.008). The CSQoL:Caregiver total scores appear negatively correlated with total number of medical issues (r = -0.549; P = 0.065). No association was found between the CSQoL:Self scores and total number of medical issues (r = -0.107; P = 0.769). Four impediments to QoL for individuals with Costello syndrome were identified: relationships outside of their immediate circle of family and friends, lack of independence, male gender, and the presence of major medical issues. This information may be useful to the families and health care professionals of adults with Costello syndrome. As a measurable characteristic, QoL may have utility as a metric in future therapeutic trials.

The Gender Medicine Team (GMT), comprised of members with expertise in endocrinology, ethics, genetics, gynecology, pediatric surgery, psychology, and urology, at Texas Children's Hospital and Baylor College of Medicine formed a task force to formulate a consensus statement on practice guidelines for managing disorders of sexual differentiation (DSD) and for making sex assignments. The GMT task force reviewed published evidence and incorporated findings from clinical experience. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the quality of evidence presented in the literature for establishing evidence-based guidelines. The task force presents a consensus statement regarding specific diagnostic and therapeutic issues in the management of individuals who present with DSD. The consensus statement includes recommendations for (1) laboratory workup, (2) acute management, (3) sex assignment in an ethical framework that includes education and involvement of the parents, and (4) surgical management.

Costello syndrome is a rare rasopathy caused by germline mutations in the oncogene HRAS resulting in increased signal transduction through the Ras/mitogen-activated protein kinase pathway. In contrast to the more common rasopathies, such as neurofibromatosis type 1 and Noonan syndrome, limited information is available on standardized cognitive testing in this cohort. Past research indicated a mean average IQ in the mild mental retardation range, with strengths in fluid reasoning (FR) and weakness in expressive language, as well as static skills over time. Here we report on standardized IQ and adaptive functioning in 18 individuals with Costello syndrome, nine males and nine females, and longitudinal development for 11 who had previous testing. The overall IQ, ranging from severe mental retardation to the average range, with a mean in the mildly mentally retarded range, was again found to be stable, but an interesting pattern in the development of nonverbal FR was identified. Participants showed an improvement in nonverbal FR, followed by stable skills thereafter, suggesting a "late bloomer" effect in late childhood/early adolescence. Overall adaptive functioning fell into the range of Intellectual Disability for 70% of subjects, with Socialization as a relative strength and Daily Living Skills an area of relative difficulty. Interestingly, females were found to be higher functioning than males in all domains, including Communication, Daily Living Skills and Socialization. Caregivers reported significantly more behavioral concerns in males, including internalizing, externalizing, and other maladaptive behaviors. In contrast, no gender differences were found in cognitive or visuomotor functioning.

Parent reported behavioral difficulties in young children are relatively common. Without adequate intervention, some children will later present with more severe problem behaviors. Parent management training is one of the best methods of treatment for behavior problems; however, existing treatments can be lengthy and difficult to conduct outside of a research setting. The Brief Behavioral Intervention was designed as a briefer version of a manualized parent management training treatment package. Thirty-one parents of children aged 2-6.5 presenting with behavior problems were included in this initial study of treatment effectiveness. Based on parent and teacher report, treatment was effective in a mean of 7.2 sessions.

Epidemiological data indicate that nearly 20% of preschool aged children have significant behavioral problems. Parents typically consult their child's primary care provider, who frequently refers to child psychologists for treatment regarding these difficulties. Psychologists skilled in providing effective services for young children are in short supply, limiting accessibility, and parents often are reluctant to follow up with a mental health specialist, suggesting low acceptability. The Behavior Consultation Clinic is a structured clinic for preschool children designed to address these issues of effectiveness, accessibility and acceptability. A retrospective review of 550 patients seen over a 5-year period found that half were seen for one therapy session. Review of the remaining patients found that slightly more than half showed improvement (32% successful discharge with improvement, 24% premature discharge with improvement) with a typical range of two to seven half-hour sessions, about a quarter did not improve, and the remaining patients were referred to a higher level of service. These data indicate that a structured, brief clinic that focuses on the needs of preschool children utilizing evidence-based approaches can be effective, acceptable, and accessible. The Behavior Consultation Clinic also serves as a training clinic for psychology interns and pediatric medical residents.

Costello syndrome is a rare congenital disorder typically characterized by severe failure-to-thrive, cardiac abnormalities including tachyarrhythmia and hypertrophic cardiomyopathy, distinctive facial features, a predisposition to papillomata and malignant tumors, neurologic abnormalities, developmental delay, and mental retardation. Its underlying cause is de novo germline mutations in the oncogene HRAS. Almost all Costello syndrome mutations affect one of the glycine residues in position 12 or 13 of the protein product. More than 80% of patients with Costello syndrome share the same underlying mutation, resulting in a G12S amino acid change. We report on two patients with novel HRAS mutations affecting amino acids 58 (T58I) and 146 (A146V), respectively. Despite facial features that appear less coarse than those typically seen in Costello patients, both patients show many of the physical and developmental problems characteristic for Costello syndrome. These novel HRAS mutations may be less common than the frequently reported G12S change, or patients with these changes may be undiagnosed due to their less coarse facial features. In addition to the findings previously known to occur in Costello syndrome, one of our patients had hypertrophic pyloric stenosis. This led us to review the medical histories on a cohort of proven HRAS mutation positive Costello syndrome patients, and we found a statistically significantly (P < 0.001) increased frequency of pyloric stenosis in Costello syndrome (5/58) compared to the general population frequency of 2-3/1,000. Thus we add hypertrophic pyloric stenosis to the abnormalities seen with increased frequency in Costello syndrome., ((c) 2008 Wiley-Liss, Inc.)

Costello syndrome encompasses pre- and postnatal medical problems including polyhydramnios, failure to thrive, cardiac complications, and an increased risk for solid tumors. Hypotonia and developmental delay are typical in infancy, and mental retardation can be diagnosed in older patients. Previous studies on the cognitive development in Costello syndrome relied on clinically diagnosed cases. The recent discovery of heterozygous HRAS mutations allows for molecular confirmation of the clinical diagnoses. We report here on cognitive abilities and adaptive behavior in the first cohort of patients with molecularly confirmed diagnoses. Further, this is the first longitudinal assessment of cognitive function in this patient population. Sixteen patients with identified HRAS mutations were tested, and 14 completed the Leiter International Performance Scale-Revised. The mean Full-Scale IQ score of 57 (range 30-87) was within the range of mild Mental Retardation. Analysis of test component subsets showed a relative strength in Fluid Reasoning with a mean score of 69 (range 48-98), in the mild range of Mental Retardation. Longitudinal analysis was performed for 12 patients by comparison of data obtained at the first evaluation (T1) to results obtained 2 years later (T2). In these patients intellectual and language abilities remained stable, and no deterioration was seen. We have thus shown that Costello syndrome is a static condition regarding intellectual and language abilities. The Leiter-R Memory Screen indicated functioning in the mildly delayed range for the majority of patients. Adaptive behavior was evaluated using the Vineland tool, and longitudinal data comparison for adaptive behavior showed improvements in Daily Living Skills, Communication, and the Adaptive Behavior Composite. However, these results must be interpreted cautiously as the measuring tool was updated from T1 to T2. Receptive language skills were measured with the Peabody Picture Vocabulary Test-III, showing a mean receptive vocabulary standard score of 65 (SD 15) in the Extremely Low range. Expressive language skills, as measured by the Expressive Vocabulary Test (EVT), scored a mean of 51 (SD 14), in the Extremely Low range. However, half of the subjects obtained the lowest possible score on the EVT, demonstrating that this is not the ideal tool for use in this patient population., ((c) 2007 Wiley-Liss, Inc.)

Costello syndrome is a rare congenital disorder whose diagnosis is based on clinical findings. The underlying genetic cause has not been identified. Common characteristics include failure to thrive, feeding problems, short stature, coarsening of facial features, developmental delay, mental retardation, skeletal problems, cardiac complications, and increased risk for solid tumors. Given its rarity, existing literature is limited regarding its natural course. Developmental milestones and intellectual functioning have never been systematically studied in this population, therefore this study focused on defining developmental and intellectual attributes. Data was obtained through solicited participation at the 3rd International Costello Syndrome Meeting. A total of 18 children (age 3-20 years) were administered the Leiter-R brief-IQ and the Peabody picture vocabulary test (PPVT)-III to assess nonverbal cognitive functioning and receptive vocabulary. Parents/guardians completed the child behavior checklist (CBCL) and participated in an interview process to complete the survey form of the Vineland adaptive behavior scales to assess emotional/behavioral issues and adaptive behavior. Results indicated that nonverbal cognitive functioning ranged from 1.5 to 4.3 SD below the age mean. Receptive vocabulary skills ranged from average functioning to 4 SD below the age mean. Adaptive behavior composites were all in the low range (2.0 to >5.0 SD below age mean), however there was significant variability in the range of domain scores. CBCL results ranged from normal to clinically significant across various clinical parameters. These data support a generalized descriptive pattern of developmental delay and mental retardation, with noted variability in receptive language, level of adaptive behavior functioning, and emotional/behavioral aspects. Skills and behavior are compared to existing literature of children with various syndromes., (Copyright 2004 Wiley-Liss, Inc.)